The overall objectives of this project are to better define the molecular mechanisms by which polypeptide growth factors can modulate proliferation of nontumorigenic mammalian cells and to define how tumorigenic cells escape from normal growth control. The unifying hypotheses upon which the experiments in this project are predicated are as follows. First, the proliferation of mammalian cells in vitro and in vivo can be controlled by the action of polypeptide growth factors. Second, inappropriate production of polypeptide growth factors by transformed cells can lead to uncontrolled growth (autocrine stimulation). Third, transformed cells may produce multiple factors that are responsible for invasion and proliferation of stromal elements (including endothelial cells) into solid tumors. One growth factor which has not been widely studied in this regard is fibroblast growth factor (FGF). Therefore, the specific aims of this project include: (1)\Expanded studies on the isolation of purified FGF from bovine pituitary glands. This will include amino acid analysis and N-terminal sequencing. (2)\Continued studies on the interaction of purified FGF with other growth factors and hormones in stimulating proliferation of nontransformed cells in a defined (serum-free) media. (3)\Development of a radioassay for FGF binding to target cells to determine the number and affinity of the putative FGF receptor. (4)\Examination of the conditioned medium from various tumor cells to determine whether transformed cells produce FGF-like molecules. (J)